In vitro lessons for wound healing

To understand a process as complex as wound healing, it is helpful to compartmentalize it. This is necessary if one is to study specific aspects individually. For the present purpose, wound healing can be subdivided into four phases: wounding, inflammation, cellular proliferation, and remodeling or maturation. Wound healing may also be considered under the temporally overlapping requirements for cellular migration, division, and differentiation or production of specialized products. Each of these discrete phenomena is potentially amenable to in vitro investigation.Recent advances in tissue culture techniques have greatly expanded the opportunity for clinically relevant, scientifically rigorous studies of wound healing. The following discussion focuses on selected applications of current methodology to this complex biologic process. It is intended to be illustrative of questions that can be addressed in vitro, not as a comprehensive review of the area.     

The human sunburn reaction: Histologic and biochemical studies

The ultraviolet-induced erythema reaction was investigated histologically and biochemically in four subjects, utilizing suction blister aspirates, analyzed for histamine and prostaglandin E₂ (PGE₂), and Epon-embedded l-μ skin biopsy sections from control skin and from irradiated skin at intervals for 72 hours after exposure to a Hanovia lamp. Major histologic alterations in the epidermis included dyskeratotic and vacuolated keratinocytes (sunburn cells), and disappearance of Langerhans cells. In the dermis the major changes were vascular, involving both the superficial and deep venular plexuses. Endothelial cell enlargement was first apparent within 30 minutes of irradiation, peaked at 24 hours, and persisted throughout the 72-hour study period. Mast cell degranulation and associated perivenular edema were first apparent at 1 hour and striking at the onset of erythema, 3 to 4 hours postirradiation; edema was absent and mast cells were again normal in number and granule content at 24 hours. Histamine levels rose approximately fourfold above control values immediately after the onset of erythema and returned to baseline within 24 hours. PGE₂ levels were statistically elevated even before the onset of erythema and reached approximately 150% of the control value at 24 hours. These data provide the first evidence that histamine may mediate the early phase of the human sunburn reaction and increase our understanding of its complex histologic and biochemical sequelae.     

Langerhans cells in normal human skin capillaries

Cells with Langerhans granules are reported for the first time in normal human skin capillaries.     

Partial genetic deficiency of the C4 component of complement in discoid lupus erythematosus and urticaria/angioedema

A high incidence of discoid lupus erythematosus (DLE) and urticaria/angioedema was found among patients with selective low levels of the C4 component of complement. Although evidence for activation of C4 was present in patients' sera, studies to determine the presence of known activation mechanisms were negative. Genetic C4 typing in four pedigrees showed that all propositi carried the null allele B^*QO. It is postulated that the low C4 levels in these patients are related to the skin lesions and this partial genetic deficiency.     

Systemic absorption of clindamycin hydrochloride after topical application

Clindamycin has become a highly popular drug for the topical therapy of acne; however, the extent to which it is systemically absorbed from the skin has has not been established. We measured the serum level and urinary excretion of clindamycin on the third day and the twenty-seventh day of therapy in thirteen patients who were applying 1% clindamycin hydrochloride topically for acne. There was no detectable antibiotic in the serum of any subject (less than 0.4 microgram/ml); in contrast, clindamycin was found in the urine of ten of the thirteen patients. There was marked intersubject variation in the urinary excretion of the drug, ranging from less than 10 to 500 micrograms/day. However, there was a highly significant correlation (p less than 0.0001) for a given subject between excretion values on days 3 and 27. There was no correlation between urinary excretion of clindamycin and either racial pigmentation or severity of acne in this relatively small group of patients. After topical application of 1% clindamycin hydrochloride, an average of 4% to 5% of clindamycin appears to be absorbed systemically, but greater amounts are absorbed in some individuals.     

Bilateral comparison of generalized lichen planus treated with psoralens and ultraviolet A

Ten patients with generalized lichen planus were treated with oral 8-methoxypsoralen photochemotherapy (PUVA) in a bilateral comparison study. Five patients (50%) cleared completely on both sides and required no maintenance treatment after a follow-up of up to 4 years. Three other patients (30%) improved at least 50% of their previous involvement. Most of the patients experienced symptomatic improvement of the treated side by the second week of the treatment. Two patients reacted adversely and exacerbated while receiving treatment to one side of the body. While preliminary, this bilateral comparison study demonstrates that PUVA is an effective therapy for generalized, symptomatic lichen planus and suggests that maintenance therapy might not be required once complete clearance is attained. Caution should be exercised, however, since some patients might develop an exacerbation of their disease with PUVA.     

Pigmentary demarcation lines associated with pregnancy

Pigmentary demarcation lines are borders of abrupt transition between more deeply pigmented skin and that of lighter pigmentation. Two patients developed these lines on the lower extremities during pregnancy.     

Role of ultraviolet A in phototherapy for psoriasis

Multiple studies have demonstrated that the doses of ultraviolet A (UVA) (320-400 nm) achieved with ultraviolet sources presently used for phototherapy for psoriasis are inadequate to induce coal tar phototoxicity (as manifested by delayed erythema). Some centers still use a phototherapy protocol that combines UVA, ultraviolet B (UVB), and tar for the treatment of generalized psoriasis. We designed a bilateral comparison study to determine whether the addition of UVA to one side, in doses sufficient to induce an immediate burning or smarting sensation in tar-treated skin, would add to the beneficial effects of UVB. The psoriasis of ten of thirteen ambulatory patients cleared in a mean of 26.1 treatments. Despite a mean cumulative UVA dose of 130.8 joules/cm2, none of the thirteen patients showed a better response on the side that received additional UVA. A "nonaggressive" inpatient protocol was designed to maximize the chances of demonstrating a beneficial effect of UVA. The psoriasis of eight of twelve patients cleared in a mean of 21.0 treatments. Despite a mean cumulative UVA dose of 40.3 joules/cm2, the twelve patients showed no difference in clearing between sides. The threshold for smarting increased throughout the treatment and provided a convenient guide to the delivery of increasing doses of UVA. In doses sufficient to induce coal tar phototoxicity manifested by the smarting reaction, UVA does not add to the known benefits of UVB phototherapy.     

Nail disorders. A review

The nail is capable of only a limited number of pathologic responses. Some of these alterations, including idiopathic disorders, infections, tumors, and drug-induced reactions, are reviewed in the light of recent observations. Whenever possible, clinicopathologic correlation has been emphasized. Specific suggestions are made for diagnostic technics and treatment modalities.     

Topical protection against long-wave ultraviolet A

A PABA ester-oxybenzone preparation is superior to PABA or sulisobenzone alone in protecting the skin from methoxsalen-induced ultraviolet A (UVA) phototoxicity after water substantivity challenge. Such a mixture would be useful as a UVA screen for uninvolved or actinically damaged skin in patients receiving psoralens and ultraviolet A (PUVA) therapy. An effective topical UVA screen also may protect against UVA-induced diseases like solar urticaria, polymorphic light eruptions, drug-induced phototoxicity or photoallergy, and possibly against the deep degenerative changes of solar elastosis.